Home » Module 5: Why Do Plants Make Drugs for Humans? » Content Background: How Do Active Compounds Get Out of the Plants?

Content Background: How Do Active Compounds Get Out of the Plants?

Basically (no pun intended!), there are several ways to get alkaloids1 out of the plants. The most efficient ways are to extract the drug2 chemically or burn the leaves, releasing the drug into the smoke. Both methods have been used for hundreds or thousands of years, and they are still used today. The efficiency of extraction by either method depends on the extent to which the drug exists in a polar3 vs non-polar4 form. Let’s focus on chemical extraction first. The extraction process consists of drying and crushing the plant. Then the crushed particles are mixed with an alkaline aqueous solution–this shifts the equilibrium in favor of the uncharged form (non-polar) of the alkaloid (this is known as the “free base”5). Remember, the alkaloid exists mainly in the charged form while it is stored in the vacuoles6. Figure 5 shows how the addition of an acid or a base shifts the equilibrium between the charged and uncharged forms of cocaine. Because the free bases are now soluble in organic solvents, they can be extracted from their watery environment with an organic solvent such as ethyl acetate or chloroform. Once the organic solvent is evaporated, there is a dry residue consisting of the basic alkaloids. Alkaloids in the free base form have a distinct advantage over the charged form (known as the acid salts because they donate a H+). They can be smoked, and that gets them to the brain faster, producing their psychoactive7 effects faster (see Module 1).

Smoking the dried and crushed leaves extracts alkaloids using similar chemical logic. First, only the free base form (non-polar) of the alkaloids, such as cocaine, morphine or nicotine, can be volatilized and released into the smoke. The free base form of alkaloids volatilizes at a lower temperature than that required to volatilize the charged form or the acid salt. (As a general rule, ionic8 compounds, such as the acidic or basic salt, have high boiling points, while covalent compounds have a low boiling point). Thus, the charged form must be heated so high, that the molecules are destroyed. Although the alkaloids exist predominantly in the polar form (within the vacuoles), there is a small amount of non-polar alkaloid that can be volatilized. The chemists in tobacco companies have taken advantage of this property of free bases. They have manipulated tobacco chemically to increase the rate and extent by which nicotine can be extracted from the burning tobacco leaves into the smoke. As discussed above, the polar form of nicotine (within the tobacco leaves) includes an extra H+ bound to the N atom. The tobacco companies add a base (ammonium hydroxide) to the tobacco leaves–this removes the extra proton and creates a non-polar form of nicotine (see Figure 5 for example), thus facilitating its volatilization and release from the cigarette into the smoke. In this way, the tobacco companies can sell more cigarettes. There is more nicotine released per gram of tobacco, so less tobacco is needed to provide the blood level of nicotine that the smoker requires to get an effect from a single cigarette. Therefore, for every bushel of tobacco harvested, more cigarettes can be manufactured and sold.

Some plants that contain non-polar compounds can be smoked to release their active ingredients without all these chemical tricks. Marijuana is a good example. Its active ingredient is THC. As discussed earlier, THC, a cannabinoid, is not an alkaloid. It does not form salts in an aqueous solution (i.e., it’s not soluble in water). Rather, THC is an oily substance; it is non-polar and extremely lipid soluble (lipophilic9). Because it exists predominantly in a non-polar form within the cannabis plant, it is easily released into the smoke produced by burning the marijuana.

Definitions:
1 an organic compound of natural origin. It contains a nitrogen atom and it is usually basic. Most alkaloids have marked pharmacological properties.
2 a substance that affects the structure or function of a cell or organism.
3 a chemical property of a substance that indicates an uneven distribution of charge within the molecule. A polar substance or drug mixes well with water but not with organic solvents and lipids. Polar or charged compounds do not cross cell membranes (lipid) very easily.
4 a chemical property of a substance that indicates an even distribution of charge within the molecule. A non-polar or non-charged compound mixes well with organic solvents and lipids but not with water.
5 the unionized form of a weak base. With reference to cocaine, it is the smokable form.
6 a sac-like compartment in a plant cell that stores alkaloids. It is responsible for “holding” various nutrients and wastes, as well as dissolving amino acids and sugars.
7 pertains to drugs that act in the brain to produce changes in mood, perceptions and behavior.
8 an atom, radical, or molecule that has gained or lost one or more electrons. Therefore it acquires a net negative or positive charge.
9 high lipid solubility. Lipophilic compounds dissolve readily in oil or organic solvent. They exist in an uncharged or non-polar form and cross biological membranes very easily.

Figures:

Figure 5 Treating the cocaine free base with HCl generates the charged form of cocaine, or the ‘acid salt’. Conversely, treating the acid salt with a base such as sodium bicarbonate (baking soda) yields the free base form of cocaine.